Prodigious therapeutic effects of combining mesenchymal stem cells with magnetic nanoparticles

Table 1 Summary of studies that used magnetic nanoparticles to improve the transplantation characteristics of mesenchymal stem cells

No.	Ref.	Magnetic nanoparticle	Source of MSCs	Application	Outcomes
1	Maggio et al[78], 2016	Iron MNP with poly(epsilon-lysine) dendrons exposing carboxybetaine residue (CB-MNP)	hBM-MSCs	Viability and differentiation	Survival, Adipogenic and osteogenic differentiation were significantly improved
2	Hu et al[79], 2021	3D printing Magnetic nanoparticles scaffold made from Ferumoxytol (γ-Fe2O3@PSC) and polylysine	AD-MSCs	Bone tissue engineering and Osteogenesis	Upregulated the MAPK signaling and PI3K-Akt signaling and increased the levels of RUNX2, ALP and SMAD 1/5/8 which promoted the Osteogenic differentiation
3	Huang et al[80], 2017	Magnetic nanoparticle composite scaffold formulated using the magnetic nanoparticles Fe2O3, Nano-hydroxyapatite and l-polylactic acid	BM-MSCs	Osteogenic differentiation of MSCs	The expression of type I collagen gene increased in MSCs with noticeable enhancement in their Osteogenic differentiation without toxic effects
4	Andrzejewska et al[30], 2019	Molday ION Rhodamine B™	hBM-MSCs	Tracking of transplanted MSCs	Basic hBM-MSC characteristics and functions might be affected by labeling. Molday ION Rhodamine B™ labeling had a better profile than other vital stains
5	Kono et al[81], 2021	Magnetic anionic liposome/atelocollagen complexes	mBM-MSCs	Sarcopenia mouse model	Magnetized MSCs have higher retention rate in the skeletal muscles after their local injection with significant enhancement in their immunomodulation abilities marked by upregulating IL-6 and IL-10 and downregulating TNF-α and IL-1β in the inflamed skeletal muscle which may be useful for effective Sarcopenia treatment
6	Guldris et al[35], 2017	(1) SPIO-PAA; (2) USPIO-PAA; and (3) USPIO-PAA-GlcN	Rat MSCs	Cell tracking by MRI	SPIO-PAA combined with polylysine showed non-homogeneous cell internalization. USPIO-PAA showed no uptake. USPIO-PAA-GlcN featured high cellular uptake, bio-compatibility, and sensitive in vitro and in vivo
7	Lee et al[36], 2010	MGIO	Primary endothelial progenitor cells	In vivo tracking of stem cells after transplantation	MGIO is an efficient label for the studying of relaxation induced by magnetic particles and cellular tracking by MRI
8	Thu et al[37], 2012	Self-assembling ferumoxytol- HPF nanocomplexes	(1) Hematopoietic stem cells; (2) Bone marrow stromal cells; and (3) Neural stem cells	Cell tracking by MRI	HPF labeling facilitates the monitoring of infused or implanted cells by MRI
9	Unterweger et al[82], 2017	Dextran-coated SPIONDex	Human endothelial and monocytic cells	MRI imaging	SPIONDex are extremely safe and represents a promising candidate for further clinical development
10	Han et al[83], 2021	3D-printed poly(lactic-co-glycolic acid) scaffolds coated with IONPs	rBM-MSCs	Rat Calvarial bone defect model to investigate Osteogenic differentiation	Increased the adhered cell number, and promoted cell spreading by upregulating the expression of integrin α1 and β1 and their downstream signaling molecules FAK and ERK1/2. ALP levels and Osteogenesis also significantly increased
11	Lee et al[43], 2009	MGIOs	Human fetal mesenchymal stem cells	MSC tracking by MRI	The use of M600 particles may be useful for cellular tracking using MRI
12	Mailänder et al[44], 2008	Carboxylated superparamagnetic iron oxide particles	MSC	Monitor trafficking of transplanted MSCs cells by MRI without transfection agents	Feasibility and efficiency of labeling MSC with SPIONs was determined
13	Dabrowska et al[46], 2018	Superparamagnetic iron oxide nanoparticles conjugated with rhodamine (Molday ION Rhodamine B™)	Human bone marrow MSCs EVs	Imaging of EVs	Molday ION is biocompatible with EVs. Labeling did not interfere with the capability of EVs to re-enter hBM-MSCs. IONs have magnetic properties useful for imaging by MRI
14	Li et al[59], 2019	Fe3O4@PDA	Rat bone marrow-derived MSCs	Migration and homing of MSCs	Iron oxide nanoparticles increased the expression of CXCR4 in MSCs and improved their homing and ant-inflammatory abilities
15	Yun et al[48], 2018	SPIONs with rhodamine B	Mouse bone marrow-derived MSCs	Enhanced homing effect in a model of olfactory injury	SPIONs-labeled MSCs produced better homing effects of MSCs in vivo
16	Meng et al[51], 2017	SPIONs (Molday ION Rhodamine B™)	WJ-MSCs	Gene carrying into cutaneous injury sites	Exposure to an external magnetic field increases transportation of SPIONs-labeled WJ-MSCs in vivo
17	Braniste et al[52], 2020	ZnFe2O nanoparticles based on iron covered with a chemically stable crystalline GaN film	Rat bone marrow MSCs	Long term monitoring of tracked MSCs	These nanoparticles are compatible with MSCs. Increasing concentrations of nanoparticles inhibit proliferation of MSCs. GaN growth on zinc ferrite nanoparticles increases the chemical stability of the material
18	Silva et al[53], 2016	Gold and maghemite nanoparticles functionalized with DMSA: (1) Au-DMSA; and (2) γ-Fe2O3-DMSA	Dental pulp derived MSCs	Tracking of MSCs in vivo	γ-Fe2O3-DMSA and Au-DMSA can be used as tracers for MSCs. Au-DMSA is not suitable for visualization and tracking. γ-Fe2O3-DMSA is a promising agent for MSC magnetic targeting
19	Moayeri et al[55], 2020	PLL hydrobromide coated SPIONs	Rat ADSC	Delivery and homing of transplanted MSCs in the target tissue	Transfection of ADSC by SPION/PLL is an appropriate protocol for cell therapy
20	Chung et al[57], 2018	Dex-IO NPs	hMSCs	Accelerate and optimize MSC therapeutics for Parkinson disease	NPs enhance the migration of hMSCs toward damaged DA-like cells, induce hMSCs to differentiate to DA-like neurons and promote the protection/regeneration effects of hMSCs
21	Li et al[84], 2020	Fe3O4@PDA NPs	Mouse bone marrow MSCs	Optimization of MSC-based therapeutic strategies for burn wound healing	NPs effectively incorporated into the MSCs without negative effects on cell properties and enhanced their migration ability
22	Dai et al[61], 2019	MIONs	mESCs	Induction of neural differentiation of stem cells	MIONs promoted the differentiation of the embryonic stem cells into nerve cells
23	Hachani et al[85], 2017	3,4-dihydroxyhydrocinnamic acid (DHCA) functionalized IONPs	hBM-MSCs	Imaging and contrast	It was significantly phagocytized by MSCs and produced significant contrast enhancement for proper tracking
24	Daquinag et al[66], 2013	Iron oxide (Fe2O3) and gold (Au) nanoparticles cross-linked with PLL	WAT ASC	WAT transplantation applications and WAT-based cell therapy	This NP-based 3D methodology potentially enhance WAT transplantation efficacy
25	Wang et al[67], 2016	Superparamagnetic Fe3O4 nanoparticles	hUCM-MSCs	Long-term banking of living cells	Magnetic induction heating in a magnetic field with Fe3O4 nanoparticles facilitates rewarming and cryopreservation outcome of hUCM-MSCs
26	Naseroleslami et al[68], 2021	SPIONs	hUCM-MSCs	Protection against myocardial injury	SPION-labeled MSCs in the presence of magnetic field reduces inflammation following myocardial injury
27	Zhang et al[69], 2020	Fe3O4@GO MNCs	Rat bone marrow mesenchymalstem cells	Bone tissue regeneration	Fe3O4@GO MNCs reduced cell damage caused by ROS, improved the activity of MSCs and promote osteogenic differentiation
28	Hamid et al[86], 2022	Combining Static Magnetic field with Samarium Cobalt (SmCO5)	hUC-MSCs	Proliferative properties o MSCs	Enhancement of MSCs proliferation without changing their stemless and immunophenotype
29	Van de Walle et al[72], 2019	Citrate coated iron oxide (maghemite) nanoparticles	hBM-MSCs	The long-term intracellular fate of MNP in MSCs and differentiation status	Intracellular de novo synthesis of magnetic nanoparticles was demonstrated due to the overexpression of H-subunit of ferritin. This process could prevent long-term cytotoxicity and enhance MSCs differentiation
30	Labusca et al[73], 2021	Fe3O4 MNP	(1) Human primary adipose derived MSCs; and (2) hWJMSCs	Cartilage engineering	Exposure to magnetic field increases ADSC-MNP chondrogenesis in ADSC, but not in WJMSC
31	Labusca et al[75], 2020	Fe3O4 magnetite MNP	Primary human ADSCs	Treatment of osteoporosis	Parameters of magnetic field and the exposure way interfere with ADSCs differentiation in terms of adipogenic and osteogenic conversion.
32	Ishmukhametov et al[87], 2022	Citrate-stabilized MNPs that are Functionalized with calf thymus DNA solution (50 μg/mL) and immobilized on glass surface	Human ADSCs	Differentiation of MSCs	Enhanced the Chondrogenesis and Osteogenesis in hTERT-transduced MSCs and the use of glass surface increased the chondrogenesis rate and reduced the need to high level of growth factors in the differentiation medium
33	Hao et al[88], 2021	Magnetic Scaffold made from Chitosan, Laponite and Fe3O4	hUC-MSCs	Proliferation and Osteogenesis	Enhanced the proliferation of hUC-MSCs and increased Osteogenesis markers; ALP, OCN and type I collagen
34	Zhang et al[89], 2022	3D magnetic scaffolds fabricated by incorporating MNPs into electrospun gelatin nanofibers coated with either citric acid or polyvinylpyrrolidone	BM-MSCs	Osteogenesis and Chondrogenesis	Chondrogenesis-related genes COL2A1 and ACAN were selectively enhanced by magnetic scaffolds with citric acid-coated MNPs (CAG). Osteogenesis-related genes (RUNX2 and SPARC were selectively upregulated by magnetic scaffolds with polyvinylpyrrolidone-coated MNPs
35	Ohki et al[90], 2020	SPIO and USPIO	hUC-MSCs	Labelling, Proliferation and differentiation	Remarkable increase in the signal intensity, proliferation and three-lineage differentiation (Osteogenesis, Adipogenesis, and Chondrogenesis)
36	Theruvath et al[91], 2021	Ferumoxytol and Ascorbic acid	BM-MSCs	Knee cartilage regeneration in minipigs	Hyaline-like cartilage regeneration in the knee joints of minipigs and improved Chondrogenesis were observed with significant upregulation in the amount of collagen type II
37	Xu et al[77], 2021	SPIOs	hUC-MSCs	Survival and Immunomodulation in Mouse Sepsis model	Enhanced the survival and immunomodulatory abilities of MSCs by increasing the levels of HO-1 and TRAF1 and promoted the polarization of macrophages to the M2 type. This was found to improve the liver- related injury in Sepsis
38	Liu et al[92], 2021	Fe3O4@PDA	hUC-MSCs	Homing and differentiation in rat model of Sciatic Nerve Chronic Compression Injury	Fe3O4@PDA-labeled MSCs showed better homing to the spinal cord under magnetic field guidance and decreases decreased spinal nerve demyelination and c-Fos expression

hBM-MSCs: Human bone marrow-derived mesenchymal stem cells; PDA: Polydopamine; SPIOs: Superparamagnetic iron oxide nanoparticles; AD-MSCs: Adipose tissue-derived mesenchymal stem cells; BM-MSCs: Bone marrow derived Mesenchymal stem cells; USPIO: Ultrasmall superparamagnetic iron oxide; MNPs: Magnetic nanoparticles; OCN: Osteocalcin; ROS: Reactive oxygen species; GO: Graphene oxide; WAT: White adipose tissue; ASC: Adipose stromal cells; MIONs: Magnetic iron oxide nanoparticles; Dex-IO NPs: Dextran-coated iron oxide nanoparticles; PLL: Poly-L-lysine; DMSA: 2,3-dimercaptosuccinic acid; WJ-MSCs: Wharton’s Jelly of the human umbilical cord-derived MSCs; EVs: Extracellular vesicles; HPF: Heparin-protamine; MGIO: Microgel iron oxide nanoparticle; MAPK: Mitogen-activated protein kinases; PI3K: Phosphatidylinositol 3-kinase; mESCs: Mouse embryonic stem cells; IL: Interleukin; TNF-α: Tumor necrosis factor-α; MRI: Magnetic resonance imaging; USPIO-PAA-GlcN: Glucosamine-modified iron oxide nanoparticles; MNC: Magnetic nanocomposites; HO-1: Heme oxygenase-1.